11:10-12:00, Rm 103

Reactive Oxygen Species and Cell SignalingS6-4The role of posttranslational modification of Oct4 in induced pluripotentstem cellsHyonchol Jang, Tae-Wan Kim, Hong-Duk YounDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799,KoreaThe study on induced pluripotent stem (iPS) cells field has been booming because of itspotential for an exciting research tool to probe mammalian development and epigeneticreprogramming as well as therapeutic potential for custom-tailored cell therapy.Reprogramming of somatic cells to iPS cells has been achieved by the expression ofseveral embryonic stem cell specific transcription factors such as Oct4, Sox2, and Klf4.To understand the signaling pathways directly regulating these factors duringreprogramming, we investigated the posttranslational modifications (PTMs) on them. Aftersetting up Oct4, Sox2, and Klf4 - driven reprogramming of mouse embryonic fibroblastsinto iPS cells, we determined the effect of PTMs on reprogramming efficiency. Inhibition ofsome PTMs by introducing point mutants of Oct4 and/or Sox2 greatly affected onreprogramming efficiency. More detailed information will be discussed in this symposium.S7-3Romo1 is a molecular bridge between TNF-αsignaling and themitochondria for ROS production that triggers TNF-α-mediated liverinjuryYoung Do YooLaboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College ofMedicine, Korea UniversityReactive oxygen species (ROS) produced by tumor necrosis factor-α(TNF-α) have animportant function in cell death by activating c-Jun N-terminal kinase. However, the exactmechanism of mitochondrial ROS production, after TNF-αstimulation, is not clearlyunderstood. In this study, we determined that ROS modulator 1 (Romo1) and B-celllymphoma-extra large (Bcl-XL) are directly associated with TNF-α-induced ROSproduction. In response to TNF-α, TNF complex II, which consists of receptor interactingprotein 1 (RIP1), TNF receptor-associated protein with death domain (TRADD), TNFreceptor-associated factor 2 (TRAF2), Fas-associated death domain protein (FADD), andpro-caspase-8, binds to the C-terminus of Romo1 located in the mitochondria.Concurrently, Romo1 recruits Bcl-XL to reduce the mitochondrial membrane potential,resulting in ROS production and apoptotic cell death. The increased cell death and DNAdamage were observed in the liver of the Romo1-transgenic mice treated with LPS (lipopolysaccharide)and D-GalN (galactosamine), compared to normal mice. On the basis ofthese results, we suggest that Romo1 is a molecular bridge between TNF-αsignaling andthe mitochondria for ROS production that triggers TNF-α-mediated apoptosis, contributingto chronic liver diseases. We also suggest that Romo1 is the novel target in thedevelopment of anti-inflammatory agents that block the origin of ROS production.S7-1Selective regulatory role of H2O2 in RTK signalingSang Won KangDepartment of Life Science, Division of Life and Pharmaceutical Sciences, Ewha WomansUniversity, Seoul 120-750, KoreaThe receptors for platelet-derived growth factor (PDGF) and vascular endothelial growthfactor (VEGF) are representative members of receptor tyrosine kinase (RTK) family.Since PDGF and VEGF are the key growth factors orchestrating mitogenic andchemoattractic responses of vascular endothelial and smooth muscle cells, respectively,both signaling pathways are coordinatelyin volved in the vascular maturation andremodeling. Here I talk about the role of H2O2 in these two RTK signaling. We havepreviously shown that a thioredoxin-dependent peroxide reductase, peroxiredoxin II (PrxII), suppresses neointimal hyperplasia of vascular smooth muscle cells by negativelyregulating PDGF signaling. Recently, we found that Prx II positively regulates VEGFsignaling in vascular endothelial cells by protecting VEGFR-2 tyrosine kinase activityagainst oxidative inactivation. As a new result, ablation of Prx II in human aorticendothelial cells results in the oxidative inactivation of VEGFR-2 tyrosine kinase.Collectively, I will present that H2O2 plays an important regulatory role in RTK signalingand PrxII is a novel reciprocal modulator in vascular cells.S7-4Regulation of NADPH oxidase in innate immunityYun Soo BaeDepartment of Life Science, Ewha Womans UniversityReactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, aregenerally considered cytotoxic. However in recent years, many reports havedemonstrated that intracellular ROS, produced in mammalian cells in response to theactivation of various receptors, serve as important second messengers in cell signaling.Recently we reported that NADPH oxidase (Nox) isozymes can be activated by toll-likereceptors (TLRs), which are key regulators of innate immunity. We showed that thestimulation of TLR4 complex with LPS as exogenous agonist or mmLDL as endogenousligand induces reactive oxygen species (ROS) generation and NF-κB activation and thatthis process is mediated by the regulation of Nox isozymes. Moreover, we demonstratedthat Nox-dependent ROS generation plays an important role in LPS- and mmLDLinducedproinflammatory cytokine production by endothelial cells (EC) and macrophages,respectively, leading to adhesion molecule expression on surface of EC and migration ofvascular cells. To extend this research, we investigated molecular connection betweenTLRs and Nox isozymes using yeast two hybrid and GST pull-down assay. In thisseminar, I will introduce and discuss the activation patterns of Nox isozymes by TLR andits pathological events.S7-2TNF signaling, ROS, and cancerZhenggang LiuCell and Cancer Biology Branch, NCI, NIH, USATumor necrosis factor (TNF) is a proinflammatory cytokine that plays a critical role indiverse cellular events, including cell proliferation, differentiation and apoptosis. TNF isalso involved in many types of diseases. The regulation of apoptosis is critical forcontrolling tissue homeostasis and Reactive Oxygen Species (ROS) generation plays akey role in the process. ROS are known to be involved in mediating TNF signaling.Recent findings on the role of ROS in regulating TNF-induced apoptosis and cancer willbe discussed. Particularly, we describe a novel HIF-1 target, ATIA (anti-TNF-inducedapoptosis), which protects cells against TNF- and hypoxia-induced apoptosis. Importantly,ATIA protects cells from apoptosis through regulating the function of the mitochondrialantioxidant enzyme, thioredoxin 2 and the generation of ROS.74 Korean Society for Biochemistry and Molecular BiologyS8-1Structural biology of ECM proteinsJihye Yun¹, Youngsil Choi², Ji-ho Yoo³, Bon-Kyung Koo¹, Hyun-Soo Cho³, Eok-Soo Oh²and Weontae Lee¹*¹Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749,Korea, ²Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for CellSignaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea, ³Departmentof Biology, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, KoreaMost of the biological function results from protein-protein/ligand interactions via their ability tocommunicate their information. The communication process in a cell has been recently studiedin the point of protein-protein or protein-lipid interactions by structural biology. NMRspectroscopy and X-ray crystallography together with biophysical techniques could be powerfulmethods in probing protein-protein interactions. The scaffold PDZ-domain containing proteinsyntenin binds to the cytoplasmic domain of syndecans, but little is known about underlyingmechanisms and the function of syntenin-1-syndecan interaction. Here we provide the evidencefor an inhibitory role of syntenin-1 on syndecan-4 functions based on structure-function analysis.Crystal structure shows that two PDZ domains of syntenin with syndecan-4 are arranged as ananti-parallel fashion, forming a symmetric dimer with a propeller shape. The syndecan dimer isexposed mostly to solvent. The structures of syntenin/syndecan/PIP2 complex forms asymmetric dimer anchored by a syndecan dimer and it provides the functional insight forsyntenin related to syndecan-4 function. Consistent to this notion, syntenin-1 decreased bindingof PKCa to syndecan-4 cytoplasmic domain via PDZ2 domain, with concomitant decrease inPKCa activity in vitro. In addition, syndecan-1 expression caused reduced FRET betweensyndecan-4 and the catalytic domain of PKCa. Furthermore, both syntenin-1 and synteninPDZ2 domain reduced PKCa localization to focal adhesions and inhibited syndecan-4-mediated functions such as focal adhesion formation and cell migration reduction.